NM_003060.4(SLC22A5):c.136C>T (p.Pro46Ser) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (9 submissions)
Last evaluated:: May 4, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000186152.44

Allele description [Variation Report for NM_003060.4(SLC22A5):c.136C>T (p.Pro46Ser)]

NM_003060.4(SLC22A5):c.136C>T (p.Pro46Ser)

Gene:

SLC22A5:solute carrier family 22 member 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.1

Genomic location:

Preferred name:

NM_003060.4(SLC22A5):c.136C>T (p.Pro46Ser)

HGVS:

NC_000005.10:g.132370108C>T
NG_008982.2:g.5405C>T
NM_001308122.2:c.136C>T
NM_003060.4:c.136C>TMANE SELECT
NP_001295051.1:p.Pro46Ser
NP_001295051.1:p.Pro46Ser
NP_003051.1:p.Pro46Ser
NC_000005.9:g.131705800C>T
NM_001308122.1:c.136C>T
NM_003060.3:c.136C>T
NM_003060.4:c.136C>T
O76082:p.Pro46Ser
p.P46S

Protein change:

P46S

Links:

UniProtKB: O76082#VAR_064113; dbSNP: rs202088921

NCBI 1000 Genomes Browser:

rs202088921

Molecular consequence:

NM_001308122.2:c.136C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003060.4:c.136C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000224397	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Aug 22, 2017)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21922592, 23430798, 17126586, 21126579 Citation Link,
SCV000239178	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 18, 2020)	germline	clinical testing	Citation Link,
SCV000609515	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 24, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001247706	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Aug 1, 2021)	germline	clinical testing	Citation Link,
SCV001740811	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV001930060	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001954236	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001973774	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV004226135	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 4, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17126586, 21126579, 28841266, 36343260, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	5	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	22	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype-phenotype correlation in primary carnitine deficiency.

Rose EC, di San Filippo CA, Ndukwe Erlingsson UC, Ardon O, Pasquali M, Longo N.

Hum Mutat. 2012 Jan;33(1):118-23. doi: 10.1002/humu.21607. Epub 2011 Oct 11.

PubMed [citation]

PMID:: 21922592
PMCID:: PMC3240685

Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency.

de Boer L, Kluijtmans LA, Morava E.

JIMD Rep. 2013;10:39-40. doi: 10.1007/8904_2012_198. Epub 2012 Dec 29.

PubMed [citation]

PMID:: 23430798
PMCID:: PMC3755582

See all PubMed Citations (7)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000224397.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	20	not provided	not provided	clinical testing	PubMed (4)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		20	not provided	not provided	not provided

From GeneDx, SCV000239178.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Carnitine transport was significantly decreased in both skin fibroblasts from patients harboring P46S and in CHO cells overexpressing P46S (Frigeni et al., 2017; Rose et al., 2012); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31980526, 30609409, 21126579, 17126586, 29614331, 29111448, 23430858, 27896095, 26828774, 28711408, 28841266, 23653224, 21922592, 20574985, 20027113, 23520115, 22989098, 23430798, 23963628)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000609515.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	0.001358	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001247706.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		5	not provided	not provided	not provided

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001740811.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001930060.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001954236.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001973774.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV004226135.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (5)

Description

PP3, PM3, PM5, PS3, PS4_moderate

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Oct 20, 2024

Relating variation to medicine